Monoclonal antibodies (MAbs) have defined several antigens associated with human carcinomas. Two of the most widely studied antigens are carcinoembryonic antigen (CEA) and TAG-72. CEA is a 180 Kd glycoprotein and TAG-72 is a high molecular weight mucin. Recent studies have demonstrated that CEA is a member of the immunoglobulin supergene family. These include CEA, normal cross-reacting antigen (NCA), biliary glycoprotein (BGP), and human pregnancy-specific beta 1-glycoprotein (SPI). No amplification of CEA-related genes was found in human colon tumor cell lines expressing high levels of CEA; however, it appeared that the CEA gene(s) were relatively hypomethylated in the CEA expressing tumor cells. We have also investigated the mechanisms responsible for up-regulation of CEA expression following the treatment of human colon tumor cell lines with recombinant human interferon gamma (Hu-IFN-gamma). The increased binding of a CEA-specific MAb to tumor cells treated with Hu-IFN-gamma correlated with increases in the steady-state levels of CEA-specific message. Recent experiments have been carried out to derive a mouse tumor cell line expressing CEA for use in both in vitro and in vivo studies. A cDNA clone encoding the human CEA gene has been isolated and subcloned into a eukaryotic expression vector. Clones expressing high levels of cell-surface CEA were isolated and preliminary characterization of the gene products has been carried out. Additional experiments will be carried out to determine the in vivo growth characteristics of clones in normal as well as athymic mice. Studies are also in progress to identify and characterize the gene(s) encoding the TAG-72 mucin antigen. Partial cDNA clones encoding mucins expressed in normal colon and colon tumors have recently been isolated.